Background: Even with antiretroviral therapy (ART), persons with HIV (PWH) experience increased morbidity and mortality. Cytomegalovirus (CMV) and Epstein--Barr virus (EBV) co-infections likely exacerbate inflammatory-related diseases. Objective: To determine if presence of detectable CMV or EBV DNA in peripheral blood mononuclear cells (PBMC) is associated with non-AIDS events among PWH receiving modern ART. Design: We performed a case--control study of PWH starting ART and HIV-suppressed at year 1 and thereafter, 140 cases who experienced non-AIDS events and 305 matched controls. Events included myocardial infarction, stroke, malignancy, serious bacterial infection or death. Methods: Blood samples were studied pre-ART, 1-year post-ART and pre-event. Controls had an event-free follow-up equal or greater than cases. CMV and EBV DNA levels were measured in PBMC. Conditional logistic regression analysis assessed associations and adjusted for relevant covariates; Spearman's correlations compared CMV and EBV DNA levels with other biomarkers. Results: CMV DNA was detected in PBMC of 25% of participants, EBV DNA was detected in more than 90%. Higher EBV DNA levels were associated with increased risk of events at all time points (odds ratio (OR) per one IQR = 1.5–1.7, all P < 0.009). At year 1, detectable CMV DNA was associated with increased risk of events in most adjusted models (OR = 1.4–1.8, P values ranging 0.03–0.17). Higher levels of CMV and EBV DNA correlated with multiple inflammatory markers and lower CD4+/CD8+ ratio. Conclusion: In PWH starting ART, detection of CMV and EBV DNA in PBMC was associated with development of non-AIDS events. Clinical trials will be needed to understand causal mechanisms and ways to interrupt them.

Rapid autopsy at the end of life in people with HIV (PWH) permits the preservation of valuable tissue specimens for subsequent study of HIV reservoirs. At our institution, we have developed a cohort of PWH who consent to a rapid autopsy to gather a wide range of fluids and tissues with the goal of advancing HIV cure research. The protocol for successfully performing these autopsies has required careful thought and development over months and years. We have now successfully performed six rapid autopsies and detail here our steps to build the study cohort, train and staff a team of more than a dozen personnel, and process and preserve hundreds of samples from each autopsy.

Background Sex differences in HIV reservoir dynamics remain under-explored. Methods Longitudinal samples from virally suppressed midlife women (N=59) and age-matched men (N=31) were analyzed retrospectively. At each time point, we measured sex hormones (by ELISA), cellular HIV DNA and RNA (by digital droplet PCR). Number of inducible HIV RNA + cells, which provides an upper estimate of replication-competent reservoir, was quantified longitudinally on a different subset of 14 women, across well-defined reproductive stages. Mixed-effects models included normalized reservoir outcomes and sex, time since ART initiation, and the sex-by-time interaction as predictors. Results At ART initiation, women and men had a median (IQR) CD4 + of 219 (82,324) cells/µl versus 248 (120, 290), median age (IQR) of 45 (42,48) versus 47 (43,51), and median follow up (IQR) of 93 (76,132) versus 74 (52,93) months. We observed a significant decline of total HIV DNA over time in both men and women (p&lt;0.01). However, the rate of change significantly differed between sexes (p&lt;0.01), with women having a significantly slower rate of decline as compared to men, more pronounced with age. By contrast, the levels of inducible HIV RNA increased incrementally over time in women during reproductive aging (&lt;0.01). Conclusions In contrast to men, where the HIV reservoir steadily declines with aging, the HIV reservoir in women is more dynamic. Total HIV DNA (including intact and defective genomes) declines more slowly in women than in men, while the inducible HIV RNA + reservoir, which is highly enriched in replication competent virus, increases in women after menopause.

Together with protective measures, routine screening for SARS-CoV-2 infection help provide a safe working environment. We evaluated a pooled nucleic acid testing strategy in a research laboratory. It allowed to maintain its activity and would save 25,920 person-hours and $1,684,800/year by increasing the margin of safety for returning to work.